ArticleThe EMBO journal2015
Crystal structures reveal transient PERK luminal domain tetramerization in endoplasmic reticulum stress signaling.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Article
- Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation.Molecules (Basel, Switzerland) · 2026Review
- Bacterial infection elicits theOpen biology · 2025Article
- ER stress tolerance is regulated by copper-dependent PERK kinase activity.Cell reports · 2025Article
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- Endoplasmic reticulum stress in non-small cell lung cancer.American journal of cancer research · 2025Review
- Cryo-EM structure of histidyl-tRNA synthetase-like domain reveals activating crossed helices at the core of GCN2.PNAS nexus · 2024Article
- Endoplasmic Reticulum Membrane Homeostasis and the Unfolded Protein Response.Cold Spring Harbor perspectives in biology · 2024Review
- Maize and heat stress: Physiological, genetic, and molecular insights.The plant genome · 2024Review
- Selenomethionine alleviates chronic heat stress-induced breast muscle injury and poor meat quality in broilers via relieving mitochondrial dysfunction and endoplasmic reticulum stress.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2024Article
- Dual RNase activity of IRE1 as a target for anticancer therapies.Journal of cell communication and signaling · 2023Review
- Article
- The Unfolded Protein Response: A Double-Edged Sword for Brain Health.Antioxidants (Basel, Switzerland) · 2023Review
- Selenoproteins synergistically protect porcine skeletal muscle from oxidative damage via relieving mitochondrial dysfunction and endoplasmic reticulum stress.Journal of animal science and biotechnology · 2023Article
- Role of ubiquitin regulatory X domain‑containing protein 3B in the development of hepatocellular carcinoma (Review).Oncology reports · 2023Review
- Signaling plasticity in the integrated stress response.Frontiers in cell and developmental biology · 2023Review
- Development of a cell-free screening assay for the identification of direct PERK activators.PloS one · 2023Article
- Alternative ATPase domain interactions in eukaryotic Hsp70 chaperones.Frontiers in molecular biosciences · 2023Review
- Review
- Signaling by the integrated stress response kinase PKR is fine-tuned by dynamic clustering.The Journal of cell biology · 2022Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Stress caused by accumulation of misfolded proteins within the endoplasmic reticulum (ER) elicits a cellular unfolded protein response (UPR) aimed at maintaining protein-folding capacity. PERK, a key upstream component, recognizes ER stress via its luminal sensor/transducer domain, but the molecular events that lead to UPR activation remain unclear. Here, we describe the crystal structures of mammalian PERK luminal domains captured in dimeric state as well as in a novel tetrameric state. Small angle X-ray scattering analysis (SAXS) supports the existence of both crystal structures also in solution. The salient feature of the tetramer interface, a helix swapped between dimers, implies transient association. Moreover, interface mutations that disrupt tetramer formation in vitro reduce phosphorylation of PERK and its target eIF2α in cells. These results suggest that transient conversion from dimeric to tetrameric state may be a key regulatory step in UPR activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.